Process for preparing clomazone, novel form and use of the same

ABSTRACT

A process for preparing clomazone is provided, the process comprising reacting 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride in an aqueous medium in the presence of a base, in particular an alkali metal hydroxide. A method for preparing clomazone is also disclosed, the method comprising (a) crystallizing clomazone from solution in an organic solvent; and (b) isolating the resulting crystals. N-benzene is a particularly suitable solvent. Further, there is provided Form I crystalline 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone (clomazone), wherein the polymorph Form I is characterized by at least one of the following properties:
         (i) an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ(+/−0.20° θ) at one or more of the following positions: about 10.63, 16.07, 18.08, 19.11, 19.34, 21.20, 24.78 and 28.80; and   (ii) an infrared (IR) spectrum having a characteristic peak: at about 2967 and 2870 cm −1 .

This application is a 371 national phase entry of PCT/CN2014/079805,filed Jun. 13, 2014, which claims benefit of GB Patent Application No.1311938.3, filed Jul. 3, 2013, the entire contents of which areincorporated herein by reference for all purposes.

BACKGROUND

1. Field

The present disclosure relates to2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone (Clomazone),an agricultural herbicide. The present disclosure relates in particularto novel crystalline polymorphs of clomazone, to processes for theirpreparation, and compositions comprising the same.

2. Description of Related Art

2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, a compoundhaving the common name clomazone, is disclosed in U.S. Pat. No.4,405,357. Its herbicidal properties are described. This herbicidalisoxazolidinone is represented by the following structural formula (I):

U.S. Pat. No. 4,405,357 discloses the preparation of clomazone. Inparticular, the following procedure to synthesize clomazone isdisclosed:

A further process scheme is disclosed in U.S. Pat. No. 4,405,357, asfollows:

However, the process yields the desired product in only a relatively lowyield due to the formation of by products having the general formulae(II) and (III) as follows:

It is disclosed in U.S. Pat. No. 4,742,176 that the typical productmixture of the above process scheme includes the compounds of formulae(I), (II) and (III) in the ratio of (I):(II):(III) of about 85/10/5. Itwould be advantageous if an improved process could be found that yieldedhigher amounts of clomazone, with reduced formation of the by-productsof formulae (II) and (III).

In addition, the process of U.S. Pat. No. 4,405,357 suffers an number ofdrawbacks. As indicated above, the reaction process utilizes methanol(MeOH) and dimethylformamide (DMF) as solvents. However, the use of theaforementioned solvents gives rise to a number of problems, inparticular on a commercial scale of production. For example, methanol isa flammable, unsafe solvent with a low flash point and is a source forperoxide formation. As a result, the use of methanol in large-scaleproduction is very limited. In addition, aprotic polar solvents, such asdimethyl formamide (DMF) are water-miscible and are typically recycledas azeotropes containing high amounts of water.

U.S. Pat. No. 4,742,176 discloses an improvement to the second processscheme of U.S. Pat. No. 4,405,357. In particular, the process ismodified by contacting the product mixture with hydrogen chloride gasprior to isolating the desired product. This treatment converts thecompound of formula (II) into a mixture of4,4-dimethyl-3-isoxazolidinone and 2-chlorobenzyl chloride, which may berecycled with base to the desired product. The compound of formula (III)in the product is converted by contact with hydrogen chloride into othercomponents, which are readily separated. Clomazone is not affected bycontact with hydrogen chloride. As will be appreciated, thesemodifications result in a greater processing complexity and involve theuse of additional components, in particular hydrogen chloride gas, whichis undesirable.

To date, there are no simple methods for the synthesis of clomazone,which can be used on a large scale to produce the desired product to ahigh degree of purity.

There is thus an urgent and unmet need in the art for efficient methodsfor the preparation and purification of clomazone , which overcome thedrawbacks and deficiencies of the prior art methods.

In addition, there are also no known crystalline polymorphic forms ofclomozone.

SUMMARY

An improved process for the preparing of clomazone has been found, theprocess avoiding the need for the solvents used in the prior artprocesses, as disclosed above, reduces the formation of side products,thereby reducing the need for extensive purification steps, and providesclomazone in high yields. The process is particularly suitable for usefor the manufacture of clomazone on a commercial scale.

In a first aspect, the invention provides a process for preparingclomazone, the process comprising:

reacting 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride inan aqueous medium in the presence of a base.

It has surprisingly been found that clomazone may be formed in highyields by the reaction of 4,4-dimethyl-3-isoxazolidinone with2-chlorobenzyl chloride in the presence of a base using water a solvent.The ability to use water is a significant advantage over the knownprocesses and avoids the need to use solvents such as methanol anddimethylformamide, discussed above. The process produces clomazone inhigh purity, avoiding the need to subject the product mixture toextensive separation techniques. Rather, it has been found thatclomazone may be recovered from the reaction mixture by simplecrystallization techniques.

In a second aspect, is provided a novel polymorph crystalline form ofclomazone, herein designated as ‘Form I’, and described in more detailbelow.

BRIEF DESCRIPTION OF DRAWINGS

The aspects and embodiments of the invention can be more clearlyunderstood by reference to the following drawings, which are intended toillustrate, but not limit, the claimed invention.

FIG. 1 is graph showing an X-ray diffractogram of the polymorphcrystalline form of clomazone (Form I) showing an infrared (IR) spectrumof the polymorph crystalline form of clomazone (Form I).

FIG. 2 is a graph showing an infrared (IR) spectrum of the polymorphcrystalline form of clomazone (Form I).

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

The reaction of 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzylchloride is conducted in an aqueous medium in the presence of a base.Suitable bases include one or a mixture of hydroxides, carbonates, andhydrides. Suitable bases include metal and ammonium compounds, withmetal compounds being preferred, in particular alkali and alkaline earthmetal bases. Alkali metal bases are particularly preferred. The base ispreferably a carbonate or hydroxide, with alkali metal carbonates andhydroxides being preferred bases. Preferred alkali metals are sodium andpotassium. Sodium hydroxide is one particularly preferred base.Potassium hydroxide is also a preferred base. Sodium carbonate andpotassium carbonate are further particularly preferred bases.

The reaction of 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzylchloride is conducted under basic conditions. Preferably, the pH of thereaction mixture is from 7.5 to 9.5, more preferably from 8.5 to 9.5.

The reaction sequence may be represented as follows:

The reaction mixture is preferably heated. Suitable temperatures are inthe range of from 50 to 95° C., more preferably from 60 to 90° C. Areaction temperature of about 85° C. has been found to be very suitable.

4,4-dimethyl-3-isoxazolidinone may be prepared by cyclizing3-chloro-N-hydroxy-2,2-dimethylpropanamide with a base. Suitable basesare those bases noted above. Again, a preferred base is an alkali metalhydroxide, in particular sodium hydroxide. It is particularly preferredto conduct the cyclizing of 3-chloro-N-hydroxy-2,2-dimethylpropanamidewith the base in a solvent, in particular in an aqueous medium usingwater as a solvent.

The cyclizing of 3-chloro-N-hydroxy-2,2-dimethylpropanamide is conductedunder basic conditions. Preferably, the pH of the reaction mixture isfrom 7.5 to 9.5.

This reaction sequence may be represented as follows:

The reaction mixture is preferably heated. Suitable temperatures are inthe range of from 20 to 60° C., more preferably from 30 to 50° C. Areaction temperature of about 45° C. has been found to be very suitable.

3-chloro-N-hydroxy-2,2-dimethylpropanamide may be prepared by thereaction of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylaminehydrochloride (NH₂OH.HCl) in the presence of a base. Suitable bases arethose bases noted above. Again, a preferred base is an alkali metalhydroxide, in particular sodium hydroxide. It is particularly preferredto conduct the reaction of 3-chloro-2,2-dimethylpropanoyl chloride withhydroxylamine hydrochloride base in the presence of a solvent, inpartiuclar an aqueous medium using water as a solvent.

The reaction of 3-chloro-2,2-dimethylpropanoyl chloride withhydroxylamine hydrochloride is conducted under basic conditions.Preferably, the pH of the reaction mixture is from 7.0 to 9.5, morepreferably from 7.0 to 8.5, still more preferably from 7.0 to 7.5.

This reaction sequence may be represented as follows:

The reaction mixture is preferably heated. Suitable temperatures are inthe range of from 50 to 95° C., more preferably from 60 to 90° C. Areaction temperature of about 85° C. has been found to be very suitable.

It is a particular advantage of the reaction scheme described above forthe preparation of clomazone from 3-chloro-2,2-dimethylpropanoylchloride that all steps in the reaction sequence may be carried out inan aqueous medium using water as a solvent, in particular for the baseemployed. It is a further advantage that the same base may be usedthroughout the aforementioned series of reactions.

As noted above, the process described hereinbefore yields clomazone inhigh yields with little formation of by-products. As a result, clomazonemay be extracted from the reaction mixture by simple crystallization,without the need for extensive separation and purification techniques.

In a further aspect, the present invention provides a method forpreparing clomazone, the method comprising:

(a) crystallizing clomazone from solution in an organic solvent; and

(b) isolating the resulting crystals.

Clomazone is barely soluble in water. However, clomazone may bedissolved into a range of organic solvents. The method of the presentinvention isolates crystals of clomazone after crystallization from asolution in an organic solvent. The method may employ a single solventor a mixture of organic solvents. Preferred solvents are organicsolvents selected from formamides, such as dimethylformamide, benzeneand substituted benzene derivatives, such as toluene, nitriles, such asacetonitrile, halogenated alkanes, such as methylene chloride, alkanes,such as hexanes, in particular n-hexane, and mixtures thereof. Thesolvent is preferably non-polar. Particularly preferred non-polarsolvents are alkanes, more preferably aliphatic alkanes, in particularnormal or straight chain alkanes. A particularly preferred solvent foruse in the method of this aspect of the present invention is an alkanehaving from 6 to 10 carbon atoms, more preferably from 6 to 8 carbonatoms, especially hexane, with n-hexane especially preferred.

In the method of the present invention, clomazone is dissolved in theorganic solvent, preferably with heating. The resulting solution iscooled and crystals of clomazone allowed to form. The crystallineproduct is then isolated from the organic solvent. Techniques andequipment for preparing the solution of clomazone in the organicsolvent, crystallizing clomazone and isolating the crystalline productare known in the art and are commercially available.

In the process of the first aspect of the present invention, clomazonemay be separated from the final reaction medium by dissolving theclomazone in the organic solvent and subjecting the resulting solutionto the method of the second aspect of the present invention.

Surprisingly, it has been found that clomazone prepared by the abovemethod of crystallization is obtained in a novel polymorph crystallineform, herein designated as ‘Form I’.

Accordingly, in a further aspect, the present invention provides Form Icrystalline 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone(clomazone), wherein the polymorph Form I is characterized by at leastone of the following properties:

(i) an X-ray powder diffraction pattern having characteristic peaksexpressed in degrees 2θ(+/−0.20° θ) at one or more of the followingpositions: about 10.63, 16.07, 18.08, 19.11, 19.34, 21.20, 24.78 and28.80; and

(ii) an infrared (IR) spectrum having a characteristic peak: at about2967 and 2870 cm⁻¹.

The X-ray powder diffraction pattern of the Form I crystalline polymorphof clomazone is shown in FIG. 1. As can be seen, Form I exhibits anX-ray powder diffraction pattern having characteristic peaks (expressedin degrees 2θ(+/−0.2° θ) at one or more of the following positions:10.63, 16.07, 18.08, 19.11, 19.34, 21.20, 24.78 and 28.80.

The infrared (IR) spectrum of Form I is shown in FIG. 2. As can be seen,Form I exhibits an infrared (IR) spectrum at the 3000 cm⁻¹ range havinga characteristic peak at about 2967 and 2870 cm⁻¹.

As noted above, Form I of clomazone is obtainable by the methoddescribed above. In particular, this form of clomazone may be obtainedby crystallization of clomazone from solution in an organic solvent,most particularly hexane, acetonitrile, methylene chloride,dimethylformamide, toluene, and mixtures thereof. Clomazone prepared bythe process and method of the present invention and Form I clomazone maybe used as a herbicide in the control of unwanted plant growth.Formulations and techniques for the use of clomazone in the control ofplant growth are known in the art.

In further aspect, the present invention provides a method ofcontrolling plant growth at a locus, the method comprising applying tothe locus a formulation comprising clomazone prepared by a process ormethod as hereinbefore described or comprising Form I clomazone.

In a still further aspect, the present invention provides the use ofclomazone prepared by a process or method as hereinbefore described orForm I clomazone in the control of plant growth.

The crystalline Form I of clomazone can be used as such, in the form ofa formulation thereof or the use forms prepared therefrom. For example,clomazone Form I may be used in the form of directly sprayablesolutions, powders, suspensions or dispersions, emulsions, oildispersions, pastes, dustable products, materials for spreading, orgranules, by means of spraying, atomizing, dusting, spreading orpouring. The use forms depend entirely on the intended purposes. Inparticular, they are intended to ensure in each case the finest possibledistribution of the active compound(s) according to the invention.

Aqueous use forms can be prepared from emulsion concentrates, pastes orwettable powders (sprayable powders, oil dispersions) by adding water.To prepare emulsions, pastes or oil dispersions, the substances, as suchor dissolved in an oil or solvent, can be homogenized in water by meansof a wetter, tackifier, dispersant or emulsifier. However, it is alsopossible to prepare concentrates composed of active substance, wetter,tackifier, dispersant or emulsifier and, if appropriate, solvent or oil,and such concentrates are suitable for dilution with water.

The active compound concentrations in the ready-to-use preparations canbe varied within relatively wide ranges. In general, they are from0.0001 to 10%, preferably from 0.01 to 1% per weight.

The following are examples of formulations of the clomazone products ofthe present invention:

1. Products for dilution with water for foliar applications. Theformulations may also be applied to seeds, either with or withoutdilution, for seed treatment purposes.

A) Water-Soluble Concentrates (SL, LS)

10 parts by weight of the active compound(s) are dissolved in 90 partsby weight of water or a water-soluble solvent. As an alternative,wetters or other auxiliaries are added. The active compound(s) dissolvesupon dilution with water, whereby a formulation with 10% (w/w) of activecompound(s) is obtained.

B) Dispersible Concentrates (DC)

20 parts by weight of the active compound(s) are dissolved in 70 partsby weight of cyclohexanone with addition of 10 parts by weight of adispersant, for example polyvinylpyrrolidone. Dilution with water givesa dispersion, whereby a formulation with 20% (w/w) of active compound(s)is obtained.

C) Emulsifiable Concentrates (EC)

15 parts by weight of the active compound(s) are dissolved in 80 partsby weight of xylene with addition of calcium dodecylbenzenesulfonate andcastor oil ethoxylate (in each case 5 parts by weight). Dilution withwater gives an emulsion, whereby a formulation with 15% (w/w) of activecompound(s) is obtained.

D) Emulsions (EW, EO, ES)

25 parts by weight of the active compound(s) are dissolved in 35 partsby weight of xylene with addition of calcium dodecylbenzenesulfonate andcastor oil ethoxylate (in each case 5 parts by weight). This mixture isintroduced into 30 parts by weight of water by means of an emulsifiermachine (e.g. Ultraturrax) and made into a homogeneous emulsion.Dilution with water gives an emulsion, whereby a formulation with 25%(w/w) of active compound(s) is obtained.

E) Suspensions (SC, OD, FS)

In an agitated ball mill, 20 parts by weight of the active compound(s)are comminuted with addition of 10 parts by weight of dispersants,wetters and 70 parts by weight of water or of an organic solvent to givea fine active compound(s) suspension. Dilution with water gives a stablesuspension of the active compound(s), whereby a formulation with 20%(w/w) of active compound(s) is obtained.

F) Water-Dispersible Granules and Water-Soluble Granules (WG, SG)

50 parts by weight of the active compound(s) are ground finely withaddition of 50 parts by weight of dispersants and wetters and made aswater-dispersible or water-soluble granules by means of technicalappliances (for example extrusion, spray tower, fluidized bed). Dilutionwith water gives a stable dispersion or solution of the activecompound(s), whereby a formulation with 50% (w/w) of active compound(s)is obtained.

G) Water-Dispersible Powders and Water-Soluble Powders (WP, SP, SS, WS)

75 parts by weight of the active compound(s) are ground in arotor-stator mill with addition of 25 parts by weight of dispersants,wetters and silica gel. Dilution with water gives a stable dispersion orsolution of the active compound(s), whereby a formulation with 75% (w/w)of active compound(s) is obtained.

H) Gel-Formulation (GF) (for Seed Treatment Purposes Only)

In an agitated ball mill, 20 parts by weight of the active compound(s)are comminuted with addition of 10 parts by weight of dispersants, 1part by weight of a gelling agent/wetters and 70 parts by weight ofwater or of an organic solvent to give a fine active compound(s)suspension. Dilution with water gives a stable suspension of the activecompound(s), whereby a formulation with 20% (w/w) of active compound(s)is obtained.

2. Products to be applied undiluted for foliar applications. For seedtreatment purposes, such products may be applied to the seed diluted.

I) Dustable Powders (DP, DS)

5 parts by weight of the active compound(s) are ground finely and mixedintimately with 95 parts by weight of finely divided kaolin. Thisformulation gives a dustable product having 5% (w/w) of activecompound(s).

J) Granules (GR, FG, GG, MG)

0.5 parts by weight of the active compound(s) is ground finely andassociated with 95.5 parts by weight of carriers, whereby a formulationwith 0.5% (w/w) of active compound(s) is obtained. Current methods forpreparing granules include extrusion, spray-drying or use of a fluidizedbed. This gives granules to be applied undiluted for foliar use.

K) Microcapsulation, ME

0.5 parts by weight of the active compound(s) is ground finely andassociated with 95.5 parts by weight of a mixture of polyurea,crosslinker, and carriers, whereby a formulation with 0.5% (w/w) ofactive compound(s) is obtained. This gives a microencapsulation producthaving 5% (w/w) of active compound(s), in which the active clomazoneingredient is encapsulated within microcapsules having a polymer shell.

L) Microcapsulation Granules, MEG

0.5 part by weight of the active compound(s) is ground finely andassociated with 95.5 parts by weight of polyurea, crosslinker, a solidcarrier and a binder to form a mixture, forming granules from theresulting mixture; applying a composition comprising a binder to coatthe granules; and drying the thus coated granules. This procedure givesa microencapsulated active ingredient within Granules having 5% (w/w) ofactive compound(s).

Embodiments of the present invention are illustrated by the followingspecific Examples.

EXAMPLES Example 1 Synthesis of Clomazone Step 1: Preparation of3-chloro-N-hydroxy-2, 2-dimethylpropanamide (CNHP)

3-chloro-N-hydroxy-2, 2-dimethylpropanamide was prepared by way of thefollowing general reaction path:

1200 kg of water was charged into a 4000 L reactor, followed by 318 kgof hydroxylamine hydrochloride (NH₂OH.HCl). The resulting mixture wasstirred at room temperature until the hydroxylamine hydrochloride wasdissolved completely in the water. 50% Sodium hydroxide aqueous solutionwas added dropwise into the reactor over a period of 1.5 h to adjust thepH to a value of from 7.0 to 7.5, with the temperature maintained at 20to 25° C. After the addition of sodium hydroxide solution was completed,713 kg of 3-chloro-2, 2-dimethylpropanoyl chloride was added dropwiseinto the reaction mixture over a period of 3 h. The reaction mixture wasstirred while maintaining the aforementioned temperature until thereaction was complete.

The resulting mixture was cooled to 5 to 10° C. and held at thistemperature with stirring for a period of 1.5 h. The resulting mixturewas filtered to isolate the solid material. The resulting solid materialwas dried under high vacuum. The resulting crude product was furtherpurified in acetone to give pure 3-chloro-N-hydroxy-2,2-dimethylpropanamide (645 kg, purity: 98%, Yield: 92%).

Step 2: Preparation of 4, 4-dimethyl-3-isoxazolidinone (010)

4, 4-dimethyl-3-isoxazolidinone was prepared from the product of Step 1by way of the following general reaction path:

1000 kg of water was charged into a 3000 L reactor then 640 kg of3-chloro-N-hydroxy-2, 2-dimethylpropanamide was added. The resultingsolution was stirred at room temperature for 1 h, and thereafter thetemperature was raised to 45° C. 50% Sodium hydroxide aqueous solutionwas added dropwise to the resulting mixture over a period of 5 hours.After the addition of sodium hydroxide was completed, the resultingmixture was stirred at room temperature until the reaction hadcompleted.

The resulting solution was cooled to 5 to 10° C. and held at thistemperature with stirring for a further 3 h. The resulting mixture wasfiltered to isolate a solid product. The solid was washed with water anddried under high vacuum to give pure 4, 4-dimethyl-3-isoxazolidinone(about 466 kg, purity: 96%: yield: 93%).

Step 3: Preparation of2-(2-chlorobenzyl)-4,4-dimethyl-1,2-oxazolidin-3-one (Clomazone)

Clomazone was prepared from the product of Step 2 by way of thefollowing general reaction path:

1000 kg of water was charged to a 4000 L reactor, then 460 kg of 4,4-dimethyl-3-isoxazolidinone was added. The resulting solution wasstirred at room temperature for 1 h. Thereafter, 383 kg of Na₂CO₃ wasadded in small portions. The temperature of the resulting mixture wasraised to 85° C. and the mixture stirred at this temperature for 2 h.Thereafter, 672 kg of 2-chlorobenzyl chloride was added dropwise over aperiod of 5 h at 85° C. After the addition was completed, the resultingsolution was stirred at the same temperature until the reaction hadcompleted.

The resulting mixture was cooled to room tempertaure and 800 kg ofdichloromethane was added to the reactor. The resulting mixture wasstirred at room temperature for 15 h. Thereafter, the aqueous phase wasseparated, extracted with dichloromethane (3 times). Dichloromethane wasrecovered by distillation and then 2000 kg of hexane was added into thereactor. The resulting mixture was refluxed for 1 h, then cooled to 10to 15° C. and stirred for another 1 h.

The solid material was isolated by filtration. The solid was washed withhexanes several times and dried under high vacuum to give pure clomazoneTechnical (815 kg, Purity: 96%).

Similar results are obtained using sodium hydroxide as the base, inplace of sodium carbonate.

Example 2 Preparation of Clomazone Form I

2 g of clomazone was heated in 10 g of hexane until completedissolution.

The resulting solution was refluxed for 1 h, then cooled to 10 to 15° C.and stirred for another 1 h. The resulting mixture was filtered toisolate a solid. The resulting solid was washed with hexanes severaltimes and dried under high vacuum to give crystals of pure clomazonetechnical (815 kg, Purity: 96%).

The crystals were characterized as being of clomazone Form I using bothinfrared (IR) spectrometry and x-ray diffraction.

The IR spectrum of the Form I clomazone is set out in FIG. 2. The IRspectrum exhibits characteristic peaks at 2967 and 2870 cm−1.

Form I clomazone has the X-ray powder diffractogram shown in FIG. 1 withthe reflexes listed in Table 1 below.

TABLE 1 2θ and d-value of modification I 2θ (°) d (Å) 10.63, ± 0.2 8.32± 0.05 16.07, ± 0.2 5.52 ± 0.03 18.08, ± 0.2 4.90 ± 0.03 19.11,. ± 0.2 4.64 ± 0.02 19.34, ± 0.2 4.59 ± 0.02 21.20, ± 0.2 4.19 ± 0.02  24.78 ±0.2 3.59 ± 0.02  28.80 ± 0.2 3.10 ± 0.02

The x-ray diffractogram was determined using the following parameters:

Wavelength

Intended wavelength type: Kα Kα1 (Å): 1.540598 Kα2 (Å): 1.544426 Kα2/Kα1intensity ratio: 0.50 Kα (Å): 1.541874 Kβ (Å): 1.392250Incident Beam Path

Radius (mm): 240.0X-ray Tube

Name: PW3373/10 Cu LFF DK185240 Anode material: Cu Voltage (kV): 40Current (mA): 40 Focus Focus type: Line Length (mm): 12.0 width (mm):0.4 Take-off angle (°): 6.0Soller Slit

Name: Soller 0.04 rad. Opening (rad.): 0.04Mask

Name: Inc. Mask Fixed 15 mm (MPD/MRD) Width (mm): 11.60Anti-Scatter Slit

Name: Slit Fixed ½° Type: Fixed Height (mm): 0.76Divergence Slit

Name: Slit Fixed 1° Distance to sample (mm): 140 Type: Fixed Height(mm): 0.38Diffracted Beam Path

Radius (mm): 240.0Anti-Scatter Slit

Name: AS Slit 5.5 mm (X′Celerator) Type: Fixed Height (mm): 5.50Filter

Name: Nickel Thickness (mm): 0.020 Material: NiDetector

Name: X′Celerator Type: RTMS detector Mode: Scanning Active length (°):2.122Source

Created by: Soochow University Application SW: X′Pert Data Collector vs.2.1a Instrument control SW: XPERT-PRO vs. 1.6 Instrument ID:0000000026005495 Scan axis: Gonio Scan range (°): 3.0150-60.0004 Stepsize (°): 0.0334 No. of points: 1705 Scan mode: Continuous

Example 3 Preparation of Form I Clomazone

2 g of clomazone prepared as described in Example 1 and 10 g ofacetonitrile were heated until complete dissolution. The resultingmixture was refluxed for 1 h, then cooled to 10 to 15° C. and stirredfor a further 1 h. The resulting mixture was filtered to isolate asolid. After filtration, the solid was washed with acetonitrile severaltimes and dried under high vacuum to give crystals of pure clomazonetechnical (815 kg, Purity: 96%). The crystals were characterized asbeing clomazone Form I using infra red spectrometry and x-raydiffraction as described in Example 2.

Example 4 Preparation of Form I Clomazone

2 g of clomazone prepared as described in Example 1 was dissolved in 10g of methylene chloride while applying low heating over a heating plate.The resulting mixture was refluxed for 1 h, then cooled to 10 to 15° C.and stirred for another 1 h. The resulting mixture was filtered toisolate a solid. After filtration, the solid was washed with methylenechloride several times and dried under high vacuum to give crystals ofpure clomazone technical (815 kg, Purity: 96%). The crystals werecharacterized as being clomazone Form I using infra red spectrometry andx-ray diffraction as described in Example 2.

Example 5 Preparation of Form I Clomazone

2 g of clomzone prepared as described in Example 1 and 10 g of dimethylformamide (DMF) were heated until complete dissolution of the clomazonewas reached. The resulting mixture was refluxed for 1 h, then cooled to10 to 15° C. and stirred for another 1 h. The resulting mixture wasfiltered to isoldate a solid. After filtration, the solid was washedwith DMF several times and dried under high vacuum to give crystals ofpure clomazone technical (815 kg, Purity: 96%). The crystals werecharacterized as being clomazone Form I using infra red spectrometry andx-ray diffraction as described in Example 2.

Example 6 Preparation of Form I Clomazone

2 g of clomzone as prepared in Example 1 and 10 g of toluene were heateduntil complete dissolution of the clomazone was reached. The resultingmixture was refluxed for 1 h, then cooled to 10 to 15° C. and stirredfor a further 1 h. Teh resulting mixture was filtered to isolate asolid. After filtration, the solid was washed with toluene several timesand dried under high vacuum to give crystals of pure clomazone technical(815 kg, Purity: 96%). The crystals were characterized as beingclomazone Form I using infra red spectrometry and x-ray diffraction asdescribed in Example 2.

Example 7 Preparation of Form I Clomazone

2 g of clomazone prepared as described in Example 1 and 10 g of an equalparts mixture of DMF and toluene were heated until complete dissolutionof the solid clomazone was reached. The resulting mixture was refluxedfor 1 h, then cooled to 10 to 15° C. and stirred for a further 1 h. Theresulting mixture was filtered to isolate a solid. After filtration, thesolid was washed with an equal parts mixture of DMF and toluene severaltimes and dried under high vacuum to give crystals of pure clomazonetechnical (815 kg, Purity: 96%). The crystals were characterized asbeing clomazone Form I using infra red spectrometry and x-raydiffraction as described in Example 2.

While certain embodiments of the invention have been illustrated anddescribed, it will be clear that the invention is not limited to theembodiments described herein. Numerous modifications, changes,variations, substitutions and equivalents will be apparent to thoseskilled in the art without departing from the spirit and scope of thepresent invention as described by the claims, which follow.

The invention claimed is:
 1. A process for preparing clomazone, the process comprising: mixing 4,4-dimethyl-3-isoxazolidinone, 2-chlorobenzyl chloride, water, and a first base to form a basic reaction mixture, and adjusting the basic reaction mixture to a pH in the range of from 7.5 to 9.5 to react 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride at the pH of from 7.5 to 9.5.
 2. The process according to claim 1, wherein the first base is selected from a hydroxide, a carbonate, a hydride or a mixture thereof.
 3. The process according to claim 1, wherein the first base is a metal base.
 4. The process according to claim 3, wherein the metal is an alkali or alkaline earth metal.
 5. The process according to claim 4, wherein the metal is sodium or potassium.
 6. The process according to claim 1, wherein the pH is in the range of from 8.5 to 9.5.
 7. The process according to claim 1, wherein the reaction of 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride is conducted at an elevated temperature.
 8. The process according to claim 7, wherein the reaction of 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride is conducted at a temperature in the range of 50 to 95° C.
 9. The process according to claim 8, wherein the reaction of 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride is conducted at a temperature in the range of from 60 to 90° C.
 10. The process according to claim 1, wherein 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride is prepared by cyclizing 3-chloro-N-hydroxy-2,2-dimethylpropanamide with a second base.
 11. The process according to claim 10, wherein the cyclizing reaction is conducted in the presence of a solvent.
 12. The process according to claim 11, wherein the solvent is water.
 13. The process according to claim 10, wherein the second base is selected from a hydroxide, a carbonate, a hydride or a mixture thereof.
 14. The process according to claim 10, wherein the second base is a metal base.
 15. The process according to claim 14, wherein the metal is an alkali or alkaline earth metal.
 16. The process according to claim 15, wherein the metal is sodium or potassium.
 17. The process according to claim 10, wherein the pH of the cyclization reaction mixture is in the range of from 7.5 to 9.5.
 18. The process according to claim 10, wherein the cyclizing reaction is conducted at an elevated temperature.
 19. The process according to claim 18, wherein the cyclizing reaction is conducted at a temperature in the range of from 20 to 60° C.
 20. The process according to claim 19, wherein the cyclizing reaction is conducted at a temperature in the range of from 30 to 50° C.
 21. The process according to claim 10, wherein 3-chloro-N-hydroxy-2,2-dimethylpropanamide is prepared by the reaction of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylamine hydrochloride in the presence of a third base.
 22. The process according to claim 21, wherein the reaction of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylamine hydrochloride is conducted in the presence of a solvent.
 23. The process according to claim 22, wherein the solvent is water.
 24. The process according to claim 21, wherein the third base is selected from a hydroxide, a carbonate, a hydride or a mixture thereof.
 25. The process according to claim 21, wherein the third base is a metal base.
 26. The process according to claim 25, wherein the metal is an alkali or alkaline earth metal.
 27. The process according to claim 26, wherein the metal is sodium or potassium.
 28. The process according to claim 21, wherein the pH of the reaction mixture of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylamine hydrochloride is in the range of from 7.0 to 9.5.
 29. The process according to claim 21, wherein the reaction of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylamine hydrochloride is conducted at an elevated temperature.
 30. The process according to claim 29, wherein the reaction of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylamine hydrochloride is conducted at a temperature in the range of from 50 to 95° C.
 31. The process according to claim 30, wherein the reaction of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylamine hydrochloride is conducted at a temperature in the range of from 60 to 90° C. 